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TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein
Citation:
Kurhanewicz, N., R. McIntosh-Kastrinsky, H. Tong, A. Ledbetter, L. Walsh, A. Farraj, AND M. Hazari. TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein. TOXICOLOGICAL AND APPLIED PHARMICOLOGY. Elsevier Science BV, Amsterdam, Netherlands, 324:51-60, (2017).
Impact/Purpose:
Ambient air pollution has been linked to adverse cardiovascular effects by numerous epidemiological, human and animal studies. In addition to “criteria” pollutant gases for which the United States Environmental Protection Agency has set National Ambient Air Quality Standards (NAAQS), non-NAAQS hazardous air pollutants (HAPs) such as acrolein are also frequently present in ambient air pollution, particularly in emissions from combustion processes including exhaust from automobiles, emissions from coal-fired power plants, and emissions from industrial sites. The results of this study demonstrate that TRPA1 channels found on airway sensory nerves, which can be described as sensors for a broad array of environmental irritants, play a role in the cardiovascular response of mice to acrolein. They provide support to the concept that air toxics in addition to NAAQS pollutants may affect cardiac outcomes and informs their risk assessment.
Description:
Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described; however, the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3ppm acrolein, 0.3ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles.
